Essay: Effects of stress and anxiety-related disorders on the brain

Abstract
This study examines previous research on the effects of stress and anxiety-related disorders on brain structures, serotonin and norepinephrine receptors. Serotonin plays a role in regulating mood and anxiety, while norepinephrine mediates the physiological symptoms of stress and anxiety, like sweat and heart rate. Stress can cause many developmental problems and cognitive deficits, as well as long term and short term physiological symptoms. During the very stressful period of adolescence, the brain and the body go through many changes. Stress can negatively impact an adolescent’s growth process as it increases the risk of many disabling disorders. This paper analyzes the effects of stress and anxiety on rats that have been exposed to a chronic stress restraint and how the two catecholamine’s, serotonin and norepinephrine, react. The amygdala and hippocampus are involved in decreasing stress and emotional processing. This paper proposes a future experiment that would trace neuronal connections in the brains of rats, stress levels, and how the exposure to a chronic restraint stress affects their behavior and physiology.
Introduction
Anxiety and stress disorders are characterized by excessive worry or fear, trouble concentrating, always anticipating the worst, irritability, and nervousness. There are many different types of anxiety disorders, as they are the most common mental health issue (National Institute of Mental Health, 2016). A person with an anxiety disorder may experience sweaty palms and shaking, upset stomach or nausea, headaches, increased heart rate, dizziness, and shortness of breath (Bystritsky, Khalsa, Cameron, & Schiffman, 2013). Unfortunately, these disorders are becoming common among the entire population. As a traumatic event or injury, experiencing a threat to your life or a loved one’s life, genetics or family history, prolonged exposure to stressful situations (i.e. public speaking, child abuse, sexual abuse, spousal abuse, etc.), and even excessive use of caffeine and tobacco have caused more of these types of disorders to occur (Culpepper, 2004). Even if an individual did not experience the stress for a long time, it still has detrimental effects on his or her neurodevelopment.
During early adolescence, a lot of developmental changes are happening throughout the whole body that can be particularly stressful such as puberty, emotional development, and brain development. The amygdala, prefrontal cortex, and hippocampus play significant roles in regulating anxiety, as well as emotion and fear (Bremner, 2006). Damage to the amygdala can cause the individual to have difficulty interpreting the emotional facial expressions and experience a reduction in fear and aggression. If there was a lesion of the hippocampus, the individual may lose the ability to form new memories, which is called anterograde amnesia. An individual with damage to the medial prefrontal cortex may be easily provoked and aggressive, as well as frustrated. Also, They show changes in emotional control, motivation, organizational skills, and inhibition (Bremner, 2013).
Often times, adolescents do not seek treatment for these traumatic events and stressors, so their problems worsen and become deeper over time. Because these disorders start to have physiological symptoms and effects on daily life, people usually start to seek help in their late 20’s. The somatic sensations, such as heart palpitations, hyperventilation, gastrointestinal problems, or other types of discomfort, are what lead these individuals to seek help (Culpepper, 2004). Culpepper (2004) noted that anxiety expresses itself neurologically through high cortisol activity. The two neurochemical systems involved in the stress response are cortisol and norepinephrine. One of the most common forms of treatment for anxiety and stress disorders is anti-anxiety medication (Bremner, 2013).
Most anti-anxiolytic medications are GABA-A positive allosteric modulators. Antidepressants used to treat anxiety disorders usually block reuptake of serotonin and norepinephrine. The primary serotonergic pathways, which originate in the raphe nuclei, modulate dopaminergic and noradrenergic pathways as well as play a fundamental role in regulating brain states, such as mood and anxiety (Bystritsky, Khalsa, Cameron, Schiffman, 2013). Not all serotonin receptor subtypes will reduce anxiolytic effects, but because of this complexity, medications that inhibit the reuptake of serotonin will result in an increase of serotonergic neurotransmission, and therefore, a reduction in anxiolytic symptoms (Bystritsky, et. al, 2013). Noradrenergic neurons are found in the locus coeruleus and project everywhere in the central nervous system. These neurons have a complex role in mediating physiological symptoms of anxiety such as heart rate, hand tremors, and quivering voice, that are triggered when individuals give a public speech (Bystritsky, et. al, 2013).
Literature Review
Researcher Bremner (2006) proposed that traumatic stress has developmental effects and changes on brain structure’s and its function. This article focused on the stress-induced changes of PTSD to specific brain regions such as the hippocampus, amygdala, and medial prefrontal cortex (Bremner, 2006). The corticotrophin-releasing factor (CRF), which is released from the hypothalamus, and the hypothalamic-pituitary-adrenal (HPA) axis play an important role in the stress response. CRF acts to mediate fear-related behaviors and triggers responses to stress. Lasting effects on the HPA axis and norepinephrine are shown in animals with early signs of stress. Thus, the researchers dechipher that These stressed animals lacked the ability to terminate the glucocorticoid response to stress, which is related to decreased glucocorticoid receptor binding in the hippocampus (Bremner, 2006). Patients with PTSD showed alterations in all these brain systems as well as the rate of neurogenesis. Treatments for PTSD, such as medications, showed an increased hippocampal volume and promotion of memory (Bremner, 2006).
Culpepper (2004) expresses how anxiety and stress are expressed through higher cortical activity, which result in somatic sensations. Many anxiety disorders are persistent and comorbid with other disorders, such as depression and schizophrenia, which leads to worse outcomes and increased medical utilization. These disorders impair the patients’ daily functioning and processing. Anti-anxiety medications have been shown to increase brain neurochemistry and functioning while also improving the condition (Culpepper, 2004). As a result, Culpepper (2004), found that patients that seek treatment earlier offset and prevent the development of comorbid disorders and improve the patient’s functional level.
Researchers Flak, Solomon, Jankord, Krause, and Herman (2012) conducted an experiment on male rats to see which regions of the brain stress affects. The subjects were randomly assigned into chronic variable stress, repeated restraint, weight-matched, and the control group. Using immunohistochemical staining to identify regions containing immunoreactive nuclei, the researchers found that the only areas with immunoreactivity was the paraventricular nucleus. Surprisingly, regions that are known to be sensitive exhibited little or no immunoreactivity, including the ventromedial hypothalamic nucleus, arcuate nucleus, and central nucleus of the amygdala (Flak et al. 2012). They found robust immunoreactivity in the hippocampus, medial prefrontal cortex, and the amygdala. As a result, it was concluded that regions, with more immunoreactivity, are important in regulating stress and sustaining and amplifying the stress response (Flak et al. 2012).
Researchers Bystritsky, Khalsa, Cameron, and Schiffman (2013) discuss symptoms of anxiety and how they change over time, the neurotransmitters affected by anxiety disorders, and the roles of pharmacological interventions. The goal of this study was the find the most appropriate ways of treating and diagnosing anxiety disorders, while also analyzing the neurobiology of these medications. The three main neurotransmitters involved in anxiety states are serotonin, norepinephrine, and dopamine (Bystritsky et al. 2013). Serotonergic pathways also modulate noradrenergic and dopaminergic, which regulate anxiolytic states. Not all serotonin receptors do regulate anxiolytic states, but despite this, medications that inhibit the reuptake of serotonin result in a reduction of anxiety symptoms. Dopamine and norepinephrine in relationship to anxiety, although complex, aid in our understanding of the impact of these neurotransmitters on the prevalance of anxiety disorders today and how this impacts us physiologically.. Dopaminergic signaling mediates feelings of self-efficacy and confidence (Bystritsky et al. 2013). Many physiological symptoms of anxiety are treated with norepinephrine and its antagonists, like propranolol. Propranolol is mainly used for physiological symptoms as it does not reduce the emotional or cognitive aspects of anxiety (Bystritsky et al. 2013).
Researchers Srikumar, Raju, and Rao (2007) focused on the learning and memory deficits that can be caused by severe stress. They conducted an experiment in which adult male rats were randomly assigned into the control or stress group. The stress group was engaged in a rodent restrainer and received ten daily injections of bromocriptine (Srikumar et al. 2007). Bromocriptine is a dopaminergic D2 receptor that has been shown to have antidepressant activity during chronic mild stress. Since it has already been examined for its effects on gastric mucosal lesions and plasma corticosterone levels, the main goal of this experiment was to test the effects on learning and memory (Srikumar, Raju, Rao, 2007). After the stress and drug treatment, the hippocampus was dissected from both groups and analyzed using isocratic ion-pair high-performance liquid chromatography. After conducting a radial arm maze, it was found that stress did, in fact, impair learning and bromocriptine reverses stress-induced impairment. Given that restraint stress decreased dopamine levels, bromocriptine significantly restored dopamine levels in the hippocampus.
The hippocampus is important for functions such as mood and memory, as well as adult neurogenesis. Researchers Parihar, Hattiangady, Kuruba, Shuai, and Shetty (2011) highlight the importance of adult neurogenesis in reducing depressive-like behavior and improved cognitive function. The goal of this study was to test the effects on unpredictable chronic stress on the hippocampus, adult neurogenesis, mood, learning, and memory. A group of male adult rats were exposed to unpredictable chronic stress for 5 minutes for 28 days (Parihar et al. 2011). Using a forced swim test and elevated plus maze, it was found that predictable chronic stress promotes antidepressant effects and reduces anxiety-related behaviors. By analyzing separate sections of the hippocampus using staining, predictable chronic stress showed no signs of neurodegeneration and enhanced the production of new cells and dendritic growth in the hippocampus. Predictable chronic stress did not alter learning, but improved memory as well as object recognition ability (Parihar et al. 2011).
Researchers Bowman and Kelly (2012) conducted an experiment to analyze the effects of chronic stress restraints on female rats. One group was exposed to the stress six hours a day for 35 days and the second group has no stress. They were both weighed weekly and tested on behavioral measures such as an open field test, object placement test, and object recognition test. Open field tests are used to test locomotor and anxiety-related behavior. Bowman and Kelly (2012) found that stressed females gained less weight, made few inner visits in the open field test, and increases in anxiety-related behaviors. Overall, the stressed females showed increases in anxiety and decreases in weight gain, but did not perform differently than the controls with regards to locomotor activity, non-spatial, or spatial memory (Bowman & Kelly, 2012). This relates back to previous studies in which increases in anxiety showed physiological symptoms, such as weight loss, but it does not explain why there is no impairment or improvement in memory and locomotor activity.
Method
Eighteen 2-4-week-old male rats will each be obtained and maintained in a standard micro-isolator cage where they will stay for eight weeks. The rats should be approximately the same age, weight, and species. They will be kept under controlled climate conditions in a vivarium kept on a 12-hour dark/light cycle. There will be an acclimation period of two weeks with free access to food and water for both the experimental and control groups. The subjects were randomly assigned to either a stress or control condition. The experimental, or stressed, group will be tied down on their backs for five hours every day for 56 days. The control group will be exposed to no stress. Both groups will be weighed weekly and observed in regard to anxiety and stress-related behaviors in an open field test. To assess effects of stress on norepinephrine and serotonin neurotransmitters, fast scan cyclic voltammetry will measure the release and uptake of the two catecholamine’s. The guide cannula will be stereotaxically placed in the anesthetized rats, of both groups, and will measure the two neurotransmitters. Once the experiment has been completed, the rats will be weighed again and observed for anxiety-related behaviors in an open field test. Results from the fast scan cyclic voltammetry test will be compared to the normal baseline levels of serotonin and norepinephrine. The effects of stress and anxiety disorders on the brain of male rats will be evaluated by an open field test and fast scan cyclic voltammetry.
Conclusion
The objective of this paper was to examine the effects of stress and anxiety-related behaviors on specific brain regions and neurotransmitters in relation to neurobiology and treatment of these disorders in male rats. Regarding previous studies, the probable outcome of this experiment would be decreased levels of serotonin in the hippocampus in the experimental group. Decreased levels of serotonin have been linked to depression and other related disorders, which is why selective serotonin reuptake inhibitors (SSRI’s) are used as antidepressants. It is expected that levels of norepinephrine will increase as it is the body’s response to stress, which will cause an increased heart rate and blood pressure. Some other changes that may be noticed are increased weight loss in the experimental group compared to the control group, as well as more anxiety-related behaviors. The results found in this experiment can also be compared with human brains and how stress and anxiety affect certain brain regions. The changes in the amygdala and hippocampus from stress can have long-term ramifications on the developmental stage of adolescence. This study analyzes the neurobiology of serotonin and norepinephrine during stress, as well as defining common symptoms, side effects, and treatments and how certain medications work inside the brain.